Elevated Tricuspid Regurgitation Jet Correlates with Decreased Brachial Artery Relaxivity In Sickle Cell Anemia Patients on Chronic Transfusion Therapy.

Vascular disease in both pulmonary and systemic vessels underlies most complications of sickle cell anemia (SCA). Multiple mechanisms contribute to this process, including inflammation, oxidative stress and decreased nitric oxide bioavailability. Chronic transfusion therapy (CTT) is thought to ameliorate some of these factors. Our goal was to determine the relationship between systemic vascular function, as indexed by flow mediated dilation (FMD), and elevated tricuspid regurgitation jet (TRJ) as a surrogate for pulmonary hypertension (PH), in chronically transfused SCA patients.

25 SCA patients on CTT were enrolled in a prospective cross sectional study between August 2008 and June 2010; the protocol was approved by our IRB. Patients were studied on the day of transfusion prior to receiving blood and then again between 24 and 120 hours post transfusion. Echocardiography, brachial artery FMD and blood sampling for CBC, reticulocyte count, LDH, plasma hemoglobin and hs-CRP were performed during each study visit. A TRJ of 2.5 m/s or higher was defined as “pulmonary hypertension” and an FMD of <8% was considered abnormal based on published data for our protocol. Pre and post transfusion data were analyzed using paired T-tests with linear regression used for univariate correlations with FMD and TRJ.

Table 1 summarizes pre and post transfusion results. A TRJ > 2.5 m/s was seen in 20% of patients pre-transfusion and in 12% post-transfusion, but this difference did not reach statistical significance. None of the patients with a TRJ < 2.5m/s pre transfusion had a TRJ > 2.5m/s post transfusion. FMD was significantly improved consequent to transfusion (5.4% to 6.8%, p<0.02) and was abnormal in 77% patients pre transfusion and in 64% post transfusion. As expected, transfusion increased Hb and hct and decreased %HbS, reticulocyte count and plasma hemoglobin; LDH and hs-CRP were unchanged. TRJ inversely correlated with FMD (r= -0.21, p=0.0014); all patients with TRJ > 2.5 m/s exhibited blunted FMD response. Abnormal TRJ and FMD correlated with elevated reticulocyte count, LDH, %Hb S, and prolonged left ventricular ejection time and isovolumic contraction time. FMD was directly correlated with hct and Hb and inversely correlated with stroke volume and cardiac output. There was a trend towards an inverse correlation of FMD with plasma hemoglobin, arginine/ ornithine ratio and high sensitivity CRP.

CTT offers incomplete protection from vascular disease in both the systemic and pulmonary beds. Patients with elevated TRJ > 2.5m/s also had abnormal FMD: both correlated with markers of hemolysis, increased %HbS as well as prolonged cardiac time intervals. Abnormal FMD, but not TRJ, was correlated with decreased Hb and hct and increased cardiac output and stroke volume, suggesting that worsening anemia affects FMD to a greater degree than TRJ. These data support the concept that pulmonary hypertension in SCA is only one manifestation of pan-systemic endothelial disease.

Coates:Novartis: Research Funding, Speakers Bureau.